COVID-19 vaccine hesitancy: assessing the prevalence, predictors, and effectiveness of a community pharmacy based counseling intervention

Background Coronavirus disease (COVID-19) vaccine hesitancy is a global challenge. In low- and middle-income countries (LMICs), the problem has persisted despite vaccine availability and decreasing infections. In Uganda, there is still limited information on the extent and predictors of vaccine hesitancy. This study sought to assess the prevalence and predictors of COVID-19 vaccine hesitancy, and the effectiveness of an intervention that involved community pharmacy counseling in combating COVID-19 vaccine hesitancy. Methods A total of 394 participants were enrolled in a 4-week prospective cohort interventional study. The study was conducted across eight community pharmacies in Mbarara City, between 9:00 AM and 5:00 PM daily. The study personnel ascertained the vaccination status of all clients seeking community pharmacy services. All unvaccinated clients were consecutively assessed for eligibility, and eligible clients were systematically enrolled after receiving the community pharmacy services for which they requested. The study intervention involved structured participant counseling (within the pharmacy premise), follow-up short message service (weekly), and telephone calls (bi-weekly). Only participants who did not accept to receive the COVID-19 vaccine despite counseling were followed up for four weeks, or until they accepted to receive a COVID-19 vaccine. The effectiveness of the community pharmacy counseling intervention was determined as an increase in COVID-19 vaccine acceptance, and desirable attitudinal change towards COVID-19 disease, vaccination exercise, and vaccines. Descriptive analysis was used to summarize data, and multivariate analysis was used to determine the predictors of COVID-19 vaccine hesitancy. A p-value < 0.05 was considered statistically significant. Results Out of 394 participants, 221 (56%) were hesitant to receive a COVID-19 vaccine. Participants expressed several reasons (mean 2±1) for COVID-19 vaccine hesitancy, mostly concerning vaccine safety (N=160, 47.3%). The overall COVID-19 vaccine acceptance rate increased by 25.4 percent points (43.9 – 69.3 percent points) after the study intervention. Age, religion, level of education, distance from the nearest public health facility, having a friend/family diagnosed with COVID-19, and personal suspicion of contracting COVID-19 were significant predictors of COVID-19 vaccine hesitancy. Conclusion COVID-19 vaccine hesitancy is a big challenge in Uganda. A mix of sociodemographic and COVID-19 vaccine perceptions are the key predictors of COVID-19 vaccine hesitancy. Although COVID-19 vaccines were not available at the time of the study, this study found that structured counseling interventions can improve COVID-19 vaccine acceptance rates. Larger prospective studies should evaluate the effectiveness of similar interventions in community pharmacies and other healthcare settings.

To achieve the national vaccination targets, integrated interventional strategies are necessary [38].The "3Cs" model [25] is among the theories advanced to explain the complex interaction of factors relating to an individual's acceptance or hesitancy towards COVID-19 vaccines.The "3C" behavioral model suggests that adoption of health services is driven by a complex interaction of Complacency, Convenience, and Confidence in the public [39][40][41].For example, concerns related to vaccine hesitancy broadly regard national vaccination programs, whereas others are specific to the context of COVID-19 and the available vaccines [39,42,43].Other established factors include risk perception of harm from the virus [44], mistrust of vaccine manufacturers [45], and credibility of the vaccine development process [46].Implying that COVID-19 mis-and disinformation may have contributed to the prevalent problem of COVID-19 vaccine hesitancy [47,48].This study therefore, is based on the "3Cs" behavioral model [25], which identifies communication as a tool and less of a determinant for successful immunization [49].Counseling and education interventions, including telephone calls and Short Message Service (SMS) reminders, have been reported to effectively dispel fear and anxieties arising from misinformation about the COVID-19 vaccines [11,50,51].In this study, we sought to determine the prevalence and predictors of COVID-19 vaccine hesitancy, as well as the effectiveness of a community pharmacy based counseling intervention.

Study design and setting
We conducted a prospective interventional study in community pharmacies within Mbarara city, between September 1 and November 30, 2022.Mbarara City is located in Mbarara district, 266 km southwest of Kampala, which is the capital city of Uganda.The current national census report indicates a total population of 195,318 within Mbarara city and 472,625 in Mbarara district.We randomly selected 8 out of 86 licensed drug outlets in Mbarara city [52].The 8 community pharmacies majorly stock and avail drugs to the general public under the supervision of a duly licensed pharmacist.

Study population, sample size, and sampling technique
We targeted all unvaccinated clients seeking community pharmacy service.All potential participants ages ≥ 18 years and consenting to participate in the study were included in the study.Participants without a mobile phone, verifiable telephone contact or residence at the time of enrolment were excluded from the study.To determine the study sample size (n), we used the single population proportion formula.Based on a nationally representative survey, a COVID-19 vaccine hesitancy prevalence of 57.8% was considered (95% CI and 5% margin of error) [33].A calculated sample size of 375 was considered.Considering a 10% non-response rate, the target sample size was 413.A Microsoft Excel 2020 random number generator was used to randomly select the 8 pharmacies from among the 86 licensed drug outlets in Mbarara city.Eligible participants were selected using a systematic random sampling method.Based on the previous month's records, the total number of clients in all the pharmacies in a month was estimated to be 5,280.A sampling interval of 12 was determined by dividing the estimated target population by the estimated sample size of 413.Thus, during the enrolment duration of 4 weeks in each of the 8 pharmacies, every twelfth client was enrolled until the intended sample size was achieved.

Research team
The intervention team consisted of 3 clinical pharmacists and 8 research assistants.The research assistants underwent extensive skills and knowledge pre-training regarding the study protocol, safety and effectiveness of the WHO approved COVID-19 vaccines currently available at the local vaccination centers in Uganda, and the key counseling points and ethical considerations on conducting research regarding COVID-19 vaccines and vaccination.

Intervention
The study intervention involved a counseling service conducted within the community pharmacy premise, and follow-up communication intervention.Communication intervention comprised of weekly short message service (SMS) and bi-weekly telephone call post enrolment.

Recruitment of participants for the intervention
The need for counseling and attitudinal assessment differed among study participants, based on the individual participant's willingness to vaccinate and the reasons for vaccine hesitancy.Counseling was tailored to the individual participant's reasons for COVID-19 vaccine hesitancy.Except for participants who were willing to receive a COVID-19 vaccine at first inquiry, counseling and attitudinal assessment were done for all participants who were not willing to be vaccinated at first questioning within the pharmacy.Only study participants who expressed interest in being vaccinated after counseling in the study site were assessed for pre-and post-intervention attitudinal assessment, whereas those who remained hesitant to receive a COVID-19 vaccine despite counseling were not assessed for a repeat attitudinal change using the collapsed 3-point Likert scale.Participant follow-up was done for 4 weeks post enrolment, among participants who remained hesitant to receive the COVID-19 vaccine despite the counseling.During the follow-up communication, participants received a customized weekly short message service (SMS), and a bi-weekly telephone call.The SMS provided reminder information regarding the benefits of COVID-19 vaccination and the availability of COVID-19 vaccines at the designated national COVID-19 vaccination centers within Mbarara city.A telephone call was only made after successful delivery of the SMS to the study participant.During the phone call, participants were counseled if they had any new concerns regarding COVID-19 vaccines.All study participants were followed up until either they accepted to receive a COVID-19 vaccine, or at the end of the study period in the fourth week.The effectiveness of the intervention was pre-determined as an increase in the vaccine acceptance rate, as well as a statistically significant difference in the pre-and postintervention participants' mean Likert scores in participant responses.

Data collection
An interviewer-administered questionnaire was iteratively developed and used it to obtain the participant's demographics and health-related data.Based on expert knowledge of study investigators, and the "3Cs" Behavioral Model of determinants of COVID-19 vaccine hesitancy [25]; a structured interview guide was developed and divided into three thematic areas, i.e., concerns regarding COVID-19 disease, COVID-19 vaccination exercise, and COVID-19 vaccines.We used a collapsed 3-point Likert scale to assess participant attitudes in the three thematic areas, before and after counseling [53].Individual participant Likert scores (responses) were categorized into three categories, i.e., Strongly Disagree/ Disagree (SD/D) (scores ≤1), Neutral/Don't know (N) (score = 2), and Strongly Agree/Agree (SA/A) (scores 3 -4).Patients were then followed up for further assessment for COVID-19 vaccine acceptance.During followup telephone calls, a structured questionnaire was used to determine the participant's acceptance of COVID-19 vaccines.All study participants were interviewed only after they received the community pharmacy service they intended to get.Participants were then interviewed/ counseled in a separate space or room within the pharmacy premises for a period not exceeding 10 minutes.Only participants who were hesitant to receive the COVID-19 vaccines were asked to provide reasons where they were hesitant to receive the vaccines.Based on the participant's attitude and concerns about the COVID-19 vaccines, counseling was provided tailored to the participant's reasons for COVID-19 vaccine hesitancy.A preand post-counseling measurement of the participant's attitude was done based on the participant's willingness to vaccinate at the first inquiry.Participant follow-up was done as described in the 'intervention' section.

Statistical analysis
Data were entered into a Microsoft Excel book sheet, and later analyzed using Statistical Package for Social Sciences software (SPSS version 21, SPSS Inc., Chicago, IL, USA).Descriptive analyses were used to summarize socio-demographic and clinical information, vaccine acceptance, reasons for vaccine hesitancy, and changes in attitude towards COVID-19 disease, vaccination and vaccines.A paired samples t-test was used to determine the mean difference between the pre-and post-intervention Likert scores.Binary logistic regression analysis was used to determine the predictors of COVID-19 vaccine hesitancy.Only variables with p-value < 0.25 at univariate level, were included in the final multivariate logistic regression model for analysis.Odds ratios were estimated at a 95% confidence interval, and p-value < 0.05 was considered statistically significant in multivariate logistic regression.

Ethical considerations
The study was approved by the Mbarara University of Science and Technology Research Ethics Committee (number: MUST-2022-567).Administrative clearance was obtained from the City clerk, Mbarara City (CR/ MC/331) to conduct research in community pharmacies.Permission was sought from the general manager of each community pharmacy prior to the study commencement.All participant information was stored on password-protected computers, only accessible by the investigators.Informed written consent was obtained from each eligible pharmacy participants prior to recruitment.
Almost all the study participants had access to COVID-19 related information (N=368, 93.7%), mainy through radio/television (N=223, 60.4%).Most participants were not aware of a friend or relative who had died of COVID-19 related complication (N=303, 76.9%).In addition, most participants had not taken any vaccine other than COVID-19 vaccines in their adult life (N=261, 66.2%), neither did they have a personal suspicion of contracting COVID-19 disease in the near past or during the study period (N=241, 61.2%).Lastly, most participants had not been diagnosed with a chronic disease in the near past (N=241, 61.2%) (Table 2).

Primary outcome: prevalence of COVID-19 vaccine hesitancy
Vaccine hesitancy was defined as participant unwillingness to receive a COVID-19 vaccine at the time of interview by the research assistant, irrespective of the participant's change of mind and willingness to receive a COVID-19 vaccine post intervention.Out of the 394 participants interviewed, over half (221, 56.0%) were hesitant to receive a COVID-19 vaccine (Fig. 1).

Secondary outcome: determine the reasons for vaccine hesitancy
Reasons for COVID-19 vaccine hesitancy were only determined among respondents who were hesitant to receive the COVID-19 vaccine at first inquiry.

Tertiary objective: predictors of COVID-19 vaccine hesitancy
All independent variables with p-value < 0.05 in the univariate analysis were subjected to a multivariate logistic regression analysis.In multivariate analysis, being an adult (age,  3).

Tertiary objective: effectiveness of a community pharmacy based counseling intervention towards COVID-19 vaccine acceptance
The COVID-19 vaccine acceptance rate was only assessed before and after the study intervention.The vaccine acceptance rate increased by 25.4 percent points by the end of the study intervention.
Out of the 394 study participant interviewed, the preintervention (baseline) COVID-19 vaccine acceptance rate was 43.9% (173/394).At the end of the study period (fourth week), the number of study participants willing to receive the COVID-19 vaccine had increased to 273, representing a post intervention COVID-19 vaccine acceptance rate of 69.3% (273/394).Therefore, the difference of the pre-and post-intervention COVID-19 vaccine acceptance rate was 25.4 percent points (Fig. 3).

Attitudinal change using a collapsed 3-point Likert scale
Overall, there was a statistically significant difference in the pre-and post-intervention Likert scores in 74.1% [20] of the questions assessing attitude towards COVID-19 disease, vaccination exercise, and vaccines (p value < 0.05) (Table 4) and (Table 5).

Discussion
The goal of this study was to explore the prevalence and predictors of hesitancy towards COVID-19 vaccines among community-dwelling adults in Mbarara City, Southwestern Uganda.The study also determined the effectiveness of a counseling intervention delivered in a community pharmacy setting.The level of hesitancy to COVID-19 vaccines was found to be high (56%) (Fig .1).The majority (N=236, 70%) of reasons for hesitancy to receive COVID-9 vaccines, were related to either the safety of vaccines (47.3%), inaccessibility of vaccines (12.4%), or individual trust in individual immunity against COVID-19 disease (10.1%) (Fig. 2).Generally, a community pharmacy based counseling intervention increased the COVID-19 vaccine acceptance rate by 25.4 percent points (43.4% -69.3%) (Fig. 3), and positively changed participants' attitude towards COVID-19 (Tables 4, 5).Age, religion, education level, distance from the nearest public health facility, having a friend/relative diagnosed with COVID-19, and personal suspicion of having contracted COVID-19 within the past 2 years,  More than half (56%) of the population in our setting was hesitant to receive the COVID-19 vaccines (Fig. 1).A findings that does not differ from the average global prevalence of COVID-19 vaccine hesitancy [32], as well as studies from rural communities in Ethiopia and India [54,55].However, our prevalence is higher than previous published surveys that reported less than 30% prevalence of COVID-19 vaccine hesitancy in Uganda [41,43]   with documented vaccine hesitancy, albeit generally low compared to the general population [56][57][58].
Interventions aimed at combating vaccine hesitancy should be anchored on contextual issues, as socioeconomic factors seem to have insignificant effects on the COVID-19 vaccine acceptance rates [20].For example, countries with minimal access to vaccines, like Ecuador and Malaysia had over 90% vaccine acceptance rates [59,60], whereas countries like France U.S with relatively better access to vaccines had lower COVID-19 acceptance rates [61].This underscores the need for cautious interpretation of research findings from different settings.
Nearly half (47.3%) of the respondents in our study reported at least one reason for vaccine hesitancy about the safety of vaccines (Fig. 2).Concerns about the safety of COVID-19 vaccines remain a major barrier to vaccine acceptance as previously reported [62,63].Other reasons included the inaccessibility of vaccines (12.4%) and individual trust in innate or acquired immunity (10.1%).Barriers to achieving equitable access to vaccines significantly differ between high and low-income countries [64].This is rather a systemic problem and not intrinsic to the individual populations.Our study like other published reports shows that individual trust in one's immunity was a common reason for vaccine hesitancy [65].As expected from the health belief model, a lower perceived risk of COVID-19 harm is associated with the COVID-19 vaccine [66].It is therefore imperative that the health authorities introduce new strategies, or revise the existing risk communication strategies as a way to minimize COVID-19 vaccine hesitancy.
We also assessed the effectiveness of a community pharmacy based counseling and communication intervention.The study intervention increased the COVID-19 vaccine acceptance rate by 25.4 percent point, from 43.9% to 69.3% (Fig. 3).This finding is evidenced by the significant attitudinal change regarding COVID-19 disease, vaccination exercise, and vaccines (p>0.05) at the study end (Table 4, 5).This COVID-19 vaccine acceptance and attitudinal outcome in our study is comparable to findings involving similar interventions, that increased COVID-19 vaccine acceptance by 21% [67].Conversely, the effectiveness of our intervention was lower compared to studies implementing similar educational/ communication interventions (84%) [51].This could be explained as due to contextual differences as the majority of the studies were conducted in English speaking high-income countries.As proposed by Bates et al., the adoption of context-relevant counseling and communication is necessary to reinforce the effect of mass sensitization campaigns, due to the diversity of reasons or barriers associated with COVID-19 vaccine hesitancy [68].There are numerous structural and systematic barriers to implementing effective public-private partnerships in resource-limited settings like, Uganda; however, this seems to be the way to go to control both current and future public health crises.
Although age has generally been identified as a key predictor of COVID-19 vaccine hesitancy [69,70], there have been contradicting findings in understanding the age category associated with COVID-19 hesitancy.However, contrary to our findings, a study by Soares et al., 3).Although some studies link low literacy with COVID-19 vaccine hesitancy [40], this finding showed the contrary.Participants resident more than 1 km from a public health facility had higher odds of being hesitant to receive COVID-19 vaccines, compared to those who lived near a public health facility (Table 3).The finding that participants who have had a friend or relative diagnosed with COVID-19 were likely to be hesitant to COVID-19 vaccines should be further interrogated; we postulate that COVID-19 disease outcomes of the friend or relative could strongly correlate to one's decision, whether to vaccinate or not.
As in previous studies [74], having a personal suspicion to have been infected with COVID-19 was associated with greater odds of being hesitant to receive a COVID-19 vaccine.As long as there is the absence of clinical or life-limiting symptoms associated with the 'suspected' COVID-19 disease, one may not appreciate the need to vaccinate.

Study strength and limitations
One of the major strengths of this study was that it involved a four-week follow-up period.Previous studies especially in our setting were largely cross-sectional.Being a prospective follow-up intervention allowed us to capture the true attitudinal change and the resultant decision to receive a vaccine within four weeks.Another strength was that the study would be generalizable to low-resource settings with similar challenges of vaccine accessibility and vaccine hesitancy.Lastly, to minimize the several potential biases, participants were informed that this was research and not part of the pharmacy services.Research assistants were trained and supervised to ensure adherence to the questionnaire to avoid question order biases.Additionally, the investigators were present at the study site at all times to ensure professional conduct and responses to the participant's concerns.Using the collapsed 3-point Likert scale as compared to the 5-point scale, minimized occurrence of extreme response bias.
Several limitations were present in our study.First, the acceptance to receive COVID-19 vaccine was based on self-reports; implying that these responses may have been influenced by social desirability bias.Secondly, the COVID-19 vaccines were not available at the time the study, thus the participant responses may have been biased as they were not expecting actual vaccination.Lastly, the perceived risk of COVID-19 was generally low at the time of the study; probably affecting the respondents' attitudes towards COVID-19, vaccines and vaccination programs.

Generalizability of results
Despite of the study limitations, the findings of the current study can be considered generalizable depending on study context and considering the strengths discussed earlier.Thus, our findings can inform future strategies in designing community pharmacy based counseling programs for vaccination campaigns.

Sensitivity analysis
No sensitivity analysis was conducted in this study.However, a step-wise backward logistic regression analysis was done to obtain the final logistic regression model.

Conclusion
COVID-19 vaccine hesitancy is a big challenge in Uganda.This study found that a combination of sociodemographic factors and COVID-19 vaccine perceptions are key predictors of COVID-19 vaccine hesitancy.Structured counseling interventions can improve COVID-19 vaccine acceptance rates.Larger prospective studies should evaluate the effectiveness of similar interventions in community pharmacies and other health care settings.pharmacies within Mbarara City, provided valuable support and guidance during the implementation of the study.These pharmacies were Byamaka Pharmaceuticals, Spela Pharmacy, Pecos Pharmacy, Rwebikoona Pharmacy, Guardian Health Pharmacy, Frepol Pharmacy, Wilbert Pharmacy, and Jey Pharmaceuticals.The research assistants, including; Andrew Atwijuka, Adella Ashaba, Davies Akampurira, Martha Haguma Inshuti played a critical role in the counseling implementation and participant follow-up.Martin Kijumi ensured timely and effective implementation of the communication intervention through SMS.

Fig. 3
Fig. 3 COVID-19 vaccine acceptance rate before and after study intervention

Table 1
Sociodemographic factors Versus COVID-19 vaccine hesitancy status among clients visiting community pharmacies in Mbarara city, southwestern Uganda

Table 3
Predictors of COVID-19 vaccine hesitancy among clients visiting community pharmacies in Mbarara city, southwestern Uganda COR Crude Odds Ratio, AOR Adjusted Odds Ratio.*p-value <0.05

Table 4
COVID-19 disease and vaccination exercise: pair mean difference (Likert scores) before and after study intervention COR Crude Ratio, AOR Adjusted Odds Ratio.*P-value <0.05.SD Standard deviation indicates that younger age was associated with vaccine hesitancy [71].COVID-19 risk perception may greatly vary across different age groups in different settings.Therefore, interventions should consider contextual factors influencing different age groups as far as COVID-19 vaccine hesitancy is concerned.The finding